Massive Parallel Phenotyping, Culturing, Assaying and Sequencing of Single Cells on an OptoSelect Chip

Recent developments in sequencing library preparation allow genomic analysis by next generation sequencing for 1,000s of individual cells. However, current technologies require abundant starting material and rarely link functional characterization and phenotypic information with sequencing results from each individual cell.
Here we present Berkeley Lights’ proprietary OptoSelect™ technology that enables precise manipulation of single cells using low-intensity visible light. For the first time, individual cells can be isolated, annotated, cultured and assayed on a single nanofluidic chip. Cells of interest can then either be exported for various downstream applications or be directly processed to generate high quality gene expression and genotyping data via our newly developed bead based sequencing preparation technology. This approach captures genomic information onto our proprietary barcoded beads that can be decoded by both our Beacon™ system and by sequencing, providing linkage between phenotypic and genomic information.
To demonstrate the flexibility of our technology, we isolated separate samples of T-cells, memory B-cells, and plasma cells as single or groups of cells on chip using light based dielectrophoreis. A series of assays were performed to further characterize the cells. The T-cells and memory B-cells were also cultured over 2-3 days. To further characterize isolated cells, we captured either mRNA, B Cell Receptor (BCR) or T Cell Receptor (TCR) sequences from each isolated and annotated single T-cell or B-cell clone. Here, we describe a new integrated protocol that precisely barcodes each single cell or clone while keeping its specific phenotypic information and allows us to generate high quality complementary genomic data.
With the capability to culture primary cells and perform various real-time functional assays, our system provides an automated and extremely flexible solution to empower research and discovery in various fields including antibody discovery and immuno-oncology.